Oral care compositions comprising zinc amino acid halides

ABSTRACT

Disclosed herein are oral care compositions comprising a zinc amino acid halide. Methods of making and using the compositions are also provided.

BACKGROUND

Dental erosion involves demineralization and damage to the toothstructure due to acid attack from nonbacterial sources. Erosion is foundinitially in the enamel and, if unchecked, may proceed to the underlyingdentin. Dental erosion may be caused or exacerbated by acidic foods anddrinks, exposure to chlorinated swimming pool water, and regurgitationof gastric acids. The tooth enamel is a negatively charged surface,which naturally tends to attract positively charged ions such ashydrogen and calcium ions, while resisting negatively charged ions suchas fluoride ions.

Dentinal hypersensitivity is acute, localized tooth pain in response tophysical stimulation of the dentine surface as by thermal (hot or cold)osmotic, tactile combination of thermal, osmotic and tactile stimulationof the exposed dentin. Exposure of the dentine, which is generally dueto recession of the gums, or loss of enamel, frequently leads tohypersensitivity. Dentinal tubules open to the surface have a highcorrelation with dentine hypersensitivity. Dentinal tubules lead fromthe pulp to the cementum. When the surface cementum of the tooth root iseroded, the dentinal tubules become exposed to the external environment.The exposed dentinal tubules provide a pathway for transmission of fluidflow to the pulpal nerves, the transmission induced by changes intemperature, pressure and ionic gradients.

While the prior art discloses the use of various oral compositions forthe treatment of dentinal hypersensitivity, dental caries, and enamelerosion and demineralization, there is still a need for additionalcompositions and methods which provide improved performance in suchtreatments.

SUMMARY

It has now been discovered that zinc ions can form a soluble complexwith an amino acid. The complex comprising zinc and amino acid andoptionally an anion and/or oxygen, forms a soluble cationic moiety,which in turn may form a salt with a halide or other anion. When placedin formulation, this complex provides an effective concentration of zincions to the enamel, thereby protecting against erosion, reducingbacterial colonization and biofilm development, and providing enhancedshine to the teeth. Moreover, upon use, the formulation provides aprecipitate that can plug the dentinal tubules, thereby reducing thesensitivity of the teeth. While providing efficient delivery of zinc incomparison to formulations with insoluble zinc salts, the formulationscomprising the zinc-amino acid complex do not exhibit the poor taste andmouthfeel, poor fluoride delivery, and poor foaming and cleaningassociated with conventional zinc-based oral care products using solublezinc salts.

In one particular embodiment, the zinc-amino acid complex is azinc-lysine-HCl complex, for example the novel complex designated ZLC,which may be formed from a mixture of zinc oxide and lysinehydrochloride. ZLC has the chemical structure [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻,and may exist in solution of the cationic cation ([Zn(C₆H₁₄N₂O₂)₂Cl]⁺)and the chloride anion, or may be a solid salt, e.g., a crystal,optionally in mono- or dihydrate form.

The invention thus provides oral care compositions, for examplemouthwash, oral gel or dentifrice compositions, that comprise azinc-amino acid complex, e.g, a zinc-lysine-chloride complex, e.g., ZLC.The compositions may optionally further comprise a fluoride source andor an additional phosphate source. The compositions may be formulated ina suitable oral care formulation e.g., a conventional dentifrice, oralgel or mouthwash base, e.g., comprising one or more abrasives,surfactants, foaming agents, vitamins, polymers, enzymes, humectants,thickeners, antimicrobial agents, preservatives, flavorings, and/orcolorants.

The invention further provides methods of using the compositions of theinvention to reduce and inhibit acid erosion of the enamel, clean theteeth, reduce bacterially-generated biofilm and plaque, reducegingivitis, inhibit tooth decay and formation of cavities, and reducedentinal hypersensitivity, comprising applying a composition of theinvention to the teeth.

The invention further provides methods of making the compositions of theinvention comprising combining a zinc ion source (e.g., ZnO), an aminoacid (e.g., a basic amino acid, e.g., arginine or lysine), andoptionally a halide source, for example combining zinc oxide and lysinehydrochloride in aqueous solution, e.g. at a molar ratio of Zn:aminoacid of 1:1 to 1:3, e.g., 1:2 and Zn:halide where present of 1:1 to 1:3,e.g., 1:2; optionally isolating the ionic complex thus formed as asolid; and admixing with an oral care base, e.g., a dentifrice, oralgel, or mouthwash base.

Further areas of applicability of the present invention will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the invention, are intended forpurposes of illustration only and are not intended to limit the scope ofthe invention.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the invention,its application, or uses.

The invention therefore provides, in a first embodiment, an oral carecomposition (Composition 1), comprising zinc in complex with an aminoacid;

e.g.,

-   -   1.1. Composition 1 wherein the amino acid is selected from        lysine, glycine and arginine, in free or orally acceptable acid        addition salt form, e.g., hydrochloride form.    -   1.2. Composition 1 or 1.1 wherein the amino acid is a basic        amino acid, e.g., arginine or lysine, in free or orally        acceptable salt form.    -   1.3. Any of the foregoing compositions further comprising a        halide in ionic association with the zinc and amino acid.    -   1.4. Any of the foregoing compositions wherein the molar ratio        of Zn:amino acid is from 3:1 to 1:5, e.g., about 1:2 and the        molar ratio of Zn:halide where present is from 3:1 to 1:3, e.g.,        about 1:2.    -   1.5. Any of the foregoing compositions wherein the zinc-amino        acid complex is formed, in whole or in part, in situ after the        composition is applied.    -   1.6. Any of the foregoing compositions wherein the zinc-amino        acid complex is formed, in whole or in part, in situ after the        composition is formulated.    -   1.7. Any of the foregoing compositions, wherein the amino acid        is lysine.    -   1.8. Any of the foregoing compositions, wherein zinc is present        in an amount of 0.05 to 10% by weight of the composition,        optionally at least 0.1, at least 0.2, at least 0.3, at least        0.4, at least 0.5, at least 1, at least 2, at least 3, or at        least 4 up to 10% by weight of the composition, e.g. about 1-3%,        e.g., about 2-2.7% by weight.    -   1.9. Any of the foregoing compositions, wherein amino acid is        present in an amount of 0.05 to 30% by weight of the        composition, optionally at least 0.1, at least 0.2, at least        0.3, at least 0.4, at least 0.5, at least 1, at least 2, at        least 3, at least 4, at least 5, at least 10, at least 15, at        least 20 up to 30% by weight, e.g., about 1-10% by weight.    -   1.10. Any of the foregoing compositions, wherein a molar ratio        of zinc to amino acid is 2:1 to 1:4, optionally 1:1 to 1:4, 1:2        to 1:4, 1:3 to 1:4, 2:1 to 1:3, 2:1 to 1:2, or 2:1 to 1:1, e.g.,        about 1:2 or 1:3    -   1.11. Any of the foregoing compositions comprising a halide in        ionic association with the zinc and amino acid, wherein the        halide is selected from the group consisting of fluorine,        chlorine, and mixtures thereof    -   1.12. Any of the foregoing compositions wherein the zinc amino        acid complex is a zinc lysine chloride complex (e.g.,        (ZnLys₂Cl)⁺ Cl⁻ or (ZnLys₃)²⁺ Cl₂) or a zinc arginine chloride        complex.    -   1.13. Any of the foregoing compositions, wherein the zinc amino        acid complex is a zinc lysine chloride complex, e.g., ZLC, e.g.,        a zinc lysine chloride complex having the chemical structure        [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻, either in solution of the cationic        cation (e.g., [Zn(C₆H₁₄N₂O₂)₂Cl]⁺) and the chloride anion, or in        solid salt form, e.g., crystal form, optionally in mono- or        dihydrate form.    -   1.14. Any of the foregoing compositions in the form of a        toothpaste, gel, mouthwash, powder, cream, strip, or gum.    -   1.15. Any of the foregoing compositions in an orally acceptable        base, e.g., a mouthwash, gel, or dentifrice base.    -   1.16. Any of the foregoing compositions in the form of a        dentifrice, e.g., wherein the zinc-amino acid complex is present        in an effective amount, e.g., in an amount of 0.5-4% by weight        of zinc, e.g., about 1-3% by weight of zinc, in a dentifrice        base.    -   1.17. Any of the foregoing compositions in the form of a        dentifrice, wherein the dentifrice base comprises an abrasive,        e.g., an effective amount of a silica abrasive, e.g., 10-30%,        e.g., about 20%.    -   1.18. Any of the foregoing compositions in the form of a        mouthwash, e.g., wherein the zinc-amino acid complex is present        in an effective amount, e.g., in an amount of 0.5-4% by weight        of zinc, e.g., about 1-3% by weight of zinc.    -   1.19. Any of the foregoing compositions further comprising an        effective amount of a fluoride ion source, e.g., providing 50 to        3000 ppm fluoride.    -   1.20. Any of the foregoing compositions further comprising an        effective amount of fluoride, e.g., wherein the fluoride is a        salt selected from stannous fluoride, sodium fluoride, potassium        fluoride, sodium monofluorophosphate, sodium fluorosilicate,        ammonium fluorosilicate, amine fluoride (e.g.,        N′-octadecyltrimethylendiamine-N,N,N′-tris(2-ethanol)-dihydrofluoride),        ammonium fluoride, titanium fluoride, hexafluorosulfate, and        combinations thereof.    -   1.21. Any of the preceding compositions comprising an effective        amount of one or more alkali phosphate salts, e.g., sodium,        potassium or calcium salts, e.g., selected from alkali dibasic        phosphate and alkali pyrophosphate salts, e.g., alkali phosphate        salts selected from sodium phosphate dibasic, potassium        phosphate dibasic, dicalcium phosphate dihydrate, calcium        pyrophosphate, tetrasodium pyrophosphate, tetrapotassium        pyrophosphate, sodium tripolyphosphate, and mixtures of any of        two or more of these, e.g., in an amount of 1-20%, e.g., 2-8%,        e.g., ca. 5%, by weight of the composition.    -   1.22. Any of the foregoing compositions comprising buffering        agents, e.g., sodium phosphate buffer (e.g., sodium phosphate        monobasic and disodium phosphate).    -   1.23. Any of the foregoing compositions comprising a humectant,        e.g., selected from glycerin, sorbitol, propylene glycol,        polyethylene glycol, xylitol, and mixtures thereof, e.g.        comprising at least 20%, e.g., 20-40%, e.g., 25-35% glycerin.    -   1.24. Any of the preceding compositions comprising one or more        surfactants, e.g., selected from anionic, cationic,        zwitterionic, and nonionic surfactants, and mixtures thereof,        e.g., comprising an anionic surfactant, e.g., a surfactant        selected from sodium lauryl sulfate, sodium ether lauryl        sulfate, and mixtures thereof, e.g. in an amount of from about        0.3% to about 4.5% by weight, e.g. 1-2% sodium lauryl sulfate        (SLS); and/or a zwitterionic surfactant, for example a betaine        surfactant, for example cocamidopropylbetaine, e.g. in an amount        of from about 0.1% to about 4.5% by weight, e.g. 0.5-2%        cocamidopropylbetaine.    -   1.25. Any of the preceding compositions further comprising a        viscosity modifying amount of one or more of polysaccharide        gums, for example xanthan gum or carrageenan, silica thickener,        and combinations thereof.    -   1.26. Any of the preceding compositions comprising gum strips or        fragments.    -   1.27. Any of the preceding compositions further comprising        flavoring, fragrance and/or coloring.    -   1.28. Any of the foregoing compositions comprising an effective        amount of one or more antibacterial agents, for example        comprising an antibacterial agent selected from halogenated        diphenyl ether (e.g. triclosan), herbal extracts and essential        oils (e.g., rosemary extract, tea extract, magnolia extract,        thymol, menthol, eucalyptol, geraniol, carvacrol, citral,        hinokitol, catechol, methyl salicylate, epigallocatechin        gallate, epigallocatechin, gallic acid, miswak extract,        sea-buckthorn extract), bisguanide antiseptics (e.g.,        chlorhexidine, alexidine or octenidine), quaternary ammonium        compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium        chloride, tetradecylpyridinium chloride (TPC),        N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic        antiseptics, hexetidine, octenidine, sanguinarine, povidone        iodine, delmopinol, salifluor, metal ions (e.g., zinc salts, for        example, zinc citrate, stannous salts, copper salts, iron        salts), sanguinarine, propolis and oxygenating agents (e.g.,        hydrogen peroxide, buffered sodium peroxyborate or        peroxycarbonate), phthalic acid and its salts, monoperthalic        acid and its salts and esters, ascorbyl stearate, oleoyl        sarcosine, alkyl sulfate, dioctyl sulfosuccinate,        salicylanilide, domiphen bromide, delmopinol, octapinol and        other piperidino derivatives, nicin preparations, chlorite        salts; and mixtures of any of the foregoing; e.g., comprising        triclosan or cetylpyridinium chloride.    -   1.29. Any of the foregoing compositions comprising an        antibacterially effective amount of triclosan, e.g. 0.1-0.5%,        e.g. about 0.3%.    -   1.30. Any of the preceding compositions further comprising a        whitening agent, e.g., a selected from the group consisting of        peroxides, metal chlorites, perborates, percarbonates,        peroxyacids, hypochlorites, and combinations thereof.    -   1.31. Any of the preceding compositions further comprising        hydrogen peroxide or a hydrogen peroxide source, e.g., urea        peroxide or a peroxide salt or complex (e.g., such as        peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or        persulphate salts; for example calcium peroxyphosphate, sodium        perborate, sodium carbonate peroxide, sodium peroxyphosphate,        and potassium persulfate);    -   1.32. Any of the preceding compositions further comprising an        agent that interferes with or prevents bacterial attachment,        e.g., solbrol or chitosan.    -   1.33. Any of the preceding compositions further comprising a        source of calcium and phosphate selected from (i) calcium-glass        complexes, e.g., calcium sodium phosphosilicates, and (ii)        calcium-protein complexes, e.g., casein phosphopeptide-amorphous        calcium phosphate    -   1.34. Any of the preceding compositions further comprising a        soluble calcium salt, e.g., selected from calcium sulfate,        calcium chloride, calcium nitrate, calcium acetate, calcium        lactate, and combinations thereof.    -   1.35. Any of the preceding compositions further comprising a        physiologically or orally acceptable potassium salt, e.g.,        potassium nitrate or potassium chloride, in an amount effective        to reduce dentinal sensitivity.    -   1.36. Any of the foregoing compositions further comprising an        anionic polymer, e.g., a synthetic anionic polymeric        polycarboxylate, e.g., wherein the anionic polymer is selected        from 1:4 to 4:1 copolymers of maleic anhydride or acid with        another polymerizable ethylenically unsaturated monomer; e.g.,        wherein the anionic polymer is a methyl vinyl ether/maleic        anhydride (PVM/MA) copolymer having an average molecular weight        (M.W.) of about 30,000 to about 1,000,000, e.g. about 300,000 to        about 800,000, e.g., wherein the anionic polymer is about 1-5%,        e.g., about 2%, of the weight of the composition.    -   1.37. Any of the preceding compositions further comprising a        breath freshener, fragrance or flavoring.    -   1.38. Any of the foregoing compositions, wherein the pH of the        composition is approximately neutral, e.g., from pH 6 to pH 8        e.g., about pH 7.    -   1.39. Any of the foregoing compositions in the form of a        mouthwash wherein the amino acid is lysine and the zinc and        lysine form a zinc-lysine-chloride complex having the chemical        structure [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻, in an amount to provide        0.5-2%, e.g., about 1% zinc by weight, the composition further        comprising humectant, e.g., sorbitol, propylene glycol and        mixtures thereof, e.g., in an amount of 10-25%, e.g., about        15-20%, non-ionic surfactant, e.g., poloxamer, e.g., in an        amount of 0.1-1%, and sweetener, flavorings, and water, e.g., a        mouthwash comprising

Ingredients Wt % Sorbitol 3-7%, e.g., about 4% ZLC to provide 0.5-2% Zn,e.g about 1% Zn Propylene Glycol 5-10%, e.g., about 7% Poloxamer, e.g.,Poloxomer 407 0.1-1%, e.g., about 0.4% Glycerin 5-10%, e.g., about 7.5%Flavor and/or sweetener 0.01-1%, e.g., about 0.1% Deionized water70-85%, e.g., about 80%

-   -   1.40. Any of the foregoing compositions in the form of an oral        gel, wherein the amino acid is lysine and the zinc and lysine        form a zinc-lysine-chloride complex having the chemical        structure [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻, in an amount to provide        0.1-2%, e.g., about 0.5% zinc by weight, and further comprising        humectant, e.g., sorbitol, propylene glycol and mixtures        thereof, e.g., in an amount of 45-65%, e.g., about 50-60%,        thickeners, e.g., cellulose derivatives, e.g., selected from        carboxymethyl cellulose (CMC), trimethyl cellulose (TMC) and        mixtures thereof, e.g., in an amount of 0.1-2%, sweetener and/or        flavorings, and water, e.g., an oral gel comprising

Ingredients Wt % Sorbitol 40-60%, e.g., 50-55% ZLC to provide 0.1-2% Zn,e.g about 0.5% Zn Carboxymethyl cellulose (CMC) and 0.5-1%, e.g., about0.7% Trimethyl cellulose (TMC) Flavoring and/or sweetener 0.01-1%Propylene Glycol 1-5%, e.g., about 3.00%

-   -   1.1. Any of the forgoing compositions for use to reduce and        inhibit acid erosion of the enamel, clean the teeth, reduce        bacterially-generated biofilm and plaque, reduce gingivitis,        inhibit tooth decay and formation of cavities, and reduce        dentinal hypersensitivity.

The invention further provides methods to reduce and inhibit aciderosion of the enamel, clean the teeth, reduce bacterially-generatedbiofilm and plaque, reduce gingivitis, inhibit tooth decay and formationof cavities, and reduce dentinal hypersensitivity, comprising applyingan effective amount of a composition of the invention, e.g., any ofComposition 1, et seq. to the teeth, and optionally then rinsing withwater or aqueous solution sufficient to trigger precipitation of zincoxide from the composition.

The invention further provides a method of making an oral carecomposition comprising a zinc amino acid complex, e.g., any ofComposition 1, et seq. comprising combining a zinc ion source with anamino acid, in free or salt form (e.g., combining zinc oxide with lysinehydrochloride), in an aqueous medium, optionally isolating the complexthus formed in solid salt form, and combining the complex with an oralcare base, e.g., a dentifrice or mouthwash base.

For example, in various embodiments, the invention provides methods toto (i) reduce hypersensitivity of the teeth, (ii) to reduce plaqueaccumulation, (iii) reduce or inhibit demineralization and promoteremineralization of the teeth, (iv) inhibit microbial biofilm formationin the oral cavity, (v) reduce or inhibit gingivitis, (vi) promotehealing of sores or cuts in the mouth, (vii) reduce levels of acidproducing bacteria, (viii) to increase relative levels of non-cariogenicand/or non-plaque forming bacteria, (ix) reduce or inhibit formation ofdental caries, (x), reduce, repair or inhibit pre-carious lesions of theenamel, e.g., as detected by quantitative light-induced fluorescence(QLF) or electrical caries measurement (ECM), (xi) treat, relieve orreduce dry mouth, (xii) clean the teeth and oral cavity, (xiii) reduceerosion, (xiv) whiten teeth; (xv) reduce tartar build-up, and/or (xvi)promote systemic health, including cardiovascular health, e.g., byreducing potential for systemic infection via the oral tissues,comprising applying any of Compositions 1, et seq. as described above tothe oral cavity of a person in need thereof, e.g., one or more times perday. The invention further provides Compositions 1, et seq. for use inany of these methods.

The invention further provides the use of zinc and an amino acid to makean oral care composition comprising a zinc amino acid complex.

The invention further provides the use of a zinc amino acid complex, forexample a zinc amino acid halide, for example a zinc-lysine-chloridecomplex, to reduce and inhibit acid erosion of the enamel, clean theteeth, reduce bacterially-generated biofilm and plaque, reducegingivitis, inhibit tooth decay and formation of cavities, and/or reducedentinal hypersensitivity.

Without intending to be bound by theory, it is believed that theformation of the zinc amino acid halide proceeds via formation of thezinc halide then coordination of amino acid residues around a centralzinc. Using reaction of ZnO with lysine hydrochloride in water as anexample, the zinc can react with lysine and/or lysine.HCl to form aclear solution of Zn-lysine-chloride complex (ZnLys₃Cl₂), wherein Zn⁺⁺is located in an octahedral center coordinated with two oxygen and twonitrogen atoms in the equatorial plane coming from two lysine'scarboxylic acids and amine groups respectively. The zinc is alsocoordinated to the third lysine via its nitrogen and carboxylic oxygen,at the apical position of the metal geometry.

In another embodiment, a zinc cation is complexes with two amino acidresidues and two chloride residues. For example, where the amino acid islysine, the complex has the formula [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻. In thiscomplex, Zn cation is coordinated by two lysine ligands with two N atomsfrom NH₂ groups and O atoms from carboxylic groups in an equatorialplane. It displays a distorted square-pyramidal geometry with the apicalposition occupied by a Cl⁻ atom. This novel structure gives rise to apositive cation moiety, to which a Cl⁻ anion is combined to form anionic salt.

Other complexes of zinc and amino acid are possible, and the preciseform is dependent in part on the molar ratios of the precursorcompounds, e.g., if there is limited halide, halide-free complexes mayform, e.g. ZnOLys₂, having a pyramid geometry, with the equatorial planethat is same as the above compound (Zn is bound to two oxygen and twonitrogen atoms from different lysines), wherein the top of the pyramidis occupied by an O atom.

Mixtures of complexes and/or additional complex structures, e.g.,involving multiple zinc ions based on the zinc structure, are possibleand contemplated within the scope of the invention. When the complexesare in solid form, they may form crystals, e.g. in hydrated form.

Irrespective of the precise structure of the complex or complexes,however, the interaction of the zinc and the amino acid convertsinsoluble zinc oxide or zinc salts to a highly soluble complex atapproximately neutral pH. With increasing dilution in water, however,the complex disassociates, and the zinc ion converts to insoluble zincoxide. This dynamic is unexpected—typically ionic compositions becomemore soluble at higher dilution, not less—and this facilitatesdeposition of the zinc precipitate on the teeth upon administration, inthe presence of saliva and with rinsing. This precipitation occludes thedentinal tubules, thereby reducing hypersensitivity, and also provideszinc to the enamel, which reduces acid erosion, biofilm and plaqueformation.

It will be understood that other amino acids can be used in place oflysine in the foregoing scheme. It will also be understood that,although the zinc, amino acid and optionally halide may be primarily inthe form of precursor materials or in the form of an ionic complex,there may be some degree of equilibrium, so that the proportion ofmaterial which is actually in complex compared to the proportion inprecursor form may vary depending on the precise conditions offormulation, concentration of materials, pH, presence or absence ofwater, presence or absence of other charged molecules, and so forth.

The actives can be delivered in the form of any oral care formulations,for example a toothpaste, gel, mouthwash, powder, cream, strip, gum, orany other known in the art.

If the actives are delivered in the form of a mouthwash, a persondesiring the benefits rinses with the stock solution and naturaldilution of the stock solution by saliva will initiate the precipitationof the zinc. Alternatively, the person can mix the stock solution withappropriate amount of an aqueous diluent, and rinse with the mixture.

In another embodiment, the mixture is prepared and immediatelytransferred into a retaining tray, such as those used in holdingwhitening gels, and the person can wear the tray for the effectiveperiod of time. The teeth that are in contact with the mixture will betreated. For use with retaining tray, the mixture can be in the form ofa low-viscosity liquid or a gel.

In another embodiment, the stock solution, or a mixture of stocksolution with water, is applied to the teeth in a gel formulation, e.g.,wherein the gel can stay on the tooth for an extended period of time foreffective treatment.

In another embodiment, the active is provided in a toothpaste. Uponbrushing, the active is diluted by saliva and water, leading toprecipitation and the formation of deposits and occluding particles.

The rate of precipitation from the formulation can be modulated byadjusting concentration of the complex in the stock solution, andchanging the ratio of the stock to water. A more diluted formula leadsto faster precipitation and is thus preferred when a fast treatment isdesired.

The benefits of the oral care compositions of the invention arenumerous. By providing zinc ions and zinc containing compounds that canrelease zinc ions in oral cavities, the oral care compositions of theinvention provide antimicrobial, antiplaque, antigingivitis,anti-malodor, anticaries, and anticalculus benefits. The occludingparticles and the surface deposits are compounds containing zinc(particularly ZnO), as well as other zinc derivatives which can releasezinc ions into oral cavities and provide the various benefits asrecognized above. Additional benefits include but are not limited toanti-attachment, anti-periodontitis and anti-bone loss, as well aspromotion of wound healing.

A second benefit is the antierosive properties of zinc ions, which formantierosive deposits on tooth surfaces through oxidation and hydrolysis.The surface deposits, as well as the occluding particles, can react withand neutralize acids, thus protecting the dental surface from theerosive effects of the acids. In this regard, the more surfacedepositions/occlusion the treatments lead to, the more efficacious thetreatments are, and therefore zinc-arginine and zinc-lysine arepreferred. It is also noted that when the surface deposits and occludingparticles neutralize acids, beneficial zinc ions and amino acids (infra)can be released, providing oral care benefits other than anti-erosion.

A third benefit is anti-sensitivity benefit as a result of theocclusion. Occlusion of dentin tubules leads to sensitivity relief.

A fourth benefit is the benefit associated with amino acids. Theoccluding particles and surface deposits contain the corresponding aminoacids, such as arginine and lysine. These amino acids provide multiplebenefits. For example, basic amino acids lead to higher pH of the plaqueand can provide anticaries benefits.

The composition can include the zinc amino acid halide and/or precursorsthereof. Precursors, which can react in situ with water to form the zincamino acid halide, include (i) zinc and an amino acid hydrohalide, or(ii) zinc chloride and amino acid, or (iii) a zinc ion source, an aminoacid, and a halogen acid, or (iv) combinations of (i), (ii), and/or(iii). In one embodiment, the zinc amino acid halide can be prepared atroom temperature by mixing the precursors in a solution, such as water.The in situ formation provides ease of formulation. The precursors canbe used instead of first having to form the zinc amino acid halide. Inanother embodiment, the water permitting formation of the zinc aminoacid halide from the precursor comes from saliva and/or rinsing waterthat comes into contact with the composition after application.

The zinc amino acid halide is a water soluble complex formed from thehalide acid addition salt of zinc (e.g., zinc chloride) and an aminoacid, or from the halide acid addition salt of an amino acid (e.g.,lysine hydrochloride) and zinc ion source, and/or from combination ofall three of a halogen acid, an amino acid, and a zinc ion source.

Examples of amino acids include, but are not limited to, the commonnatural amino acids, e.g.: lysine, arginine, histidine, glycine, serine,threonine, asparagine, glutamine, cysteine, selenocysteine, proline,alanine, valine, isoleucine, leucine, methionine, phenylalanine,tyrosine, tryptophan, aspartic acid, and glutamic acid. In someembodiments the amino acid is a neutral or acidic amino acid, e.g.,glycine.

As seen from the examples below, the precipitation of zinc from thecomplex upon dilution with water is most notable when the complex isformed from a basic amino acid. Thus, where precipitation upon dilutionis desired, a basic amino acid may be preferred. In some embodiments,therefore, the amino acid is a basic amino acid. By “basic amino acid”is meant the naturally occurring basic amino acids, such as arginine,lysine, and histidine, as well as any basic amino acid having a carboxylgroup and an amino group in the molecule, which is water-soluble andprovides an aqueous solution with a pH of about 7 or greater.Accordingly, basic amino acids include, but are not limited to,arginine, lysine, citrulline, ornithine, creatine, histidine,diaminobutanoic acid, diaminoproprionic acid, salts thereof orcombinations thereof. In certain embodiments, the amino acid is lysine.In other embodiments, the amino acid is arginine.

The halide may be chlorine, bromine, or iodine, most typically chlorine.The acid addition salt of an amino acid and a halogen acid (e.g., HCl,HBr, or HI) is sometimes referred to herein as an amino acidhydrohalide. Thus one example of an amino acid hydrohalide is lysinehydrochloride. Another is glycine hydrochloride.

The zinc ion source for combination with an amino acid halide or anamino acid optionally plus halogen acid in this case may be, e.g., zincoxide or zinc chloride.

In certain embodiments, the amount of zinc amino acid halide in thecomposition is 0.05 to 10% by weight of the composition. In certainembodiments, precursors, e.g., zinc and amino acid hydrohalide, arepresent in amounts such that when combined into the zinc amino acidhalide, the zinc amino acid halide would be present in an amount of 0.05to 10% by weight of the composition. In either of these embodiments, theamount of the zinc amino acid halide can be varied for the desiredpurpose, such as a dentifrice or a mouthwash. In other embodiments, theamount of the zinc amino acid halide is at least 0.1, at least 0.2, atleast 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least3, or at least 4 up to 10% by weight of the composition. In otherembodiments, the amount of the zinc amino acid halide is less than 9,less than 8, less than 7, less than 6, less than 5, less than 4, lessthan 3, less than 2, less than 1, less than 0.5 to 0.05% by weight ofthe composition. In other embodiments, the amounts are 0.05 to 5%, 0.05to 4%, 0.05 to 3%, 0.05 to 2%, 0.1 to 5%, 0.1 to 4%, 0.1 to 3%, 0.1 to2%, 0.5 to 5%, 0.5 to 4%, 0.5 to 3%, or 0.5 to 2% by weight of thecomposition.

In certain embodiments, zinc is present in an amount of 0.05 to 10% byweight of the composition. In other embodiments, the amount of zinc isat least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, atleast 1, at least 2, at least 3, or at least 4 up to 10% by weight ofthe composition. In other embodiments, the amount of the zinc is lessthan 9, less than 8, less than 7, less than 6, less than 5, less than 4,less than 3, less than 2, less than 1, less than 0.5 to 0.05% by weightof the composition. In other embodiments, the amounts are 0.05 to 5%,0.05 to 4%, 0.05 to 3%, 0.05 to 2%, 0.1 to 5%, 0.1 to 4%, 0.1 to 3%, 0.1to 2%, 0.5 to 5%, 0.5 to 4%, 0.5 to 3%, or 0.5 to 2% by weight of thecomposition.

In certain embodiments, amino acid hydrohalide is is present in anamount of 0.05 to 30% by weight. In other embodiments, the amount is atleast 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, atleast 1, at least 2, at least 3, at least 4, at least 5, at least 10, atleast 15, at least 20 up to 30% by weight. In other embodiments, theamount is less than 30, less than 25, less than 20, less than 15, lessthan 10, less than 5, less than 4, less than 3, less than 2, or lessthan 1 down to 0.05% by weight of the composition.

Where precursor materials are present, they are preferably present inmolar ratios approximately as required to produce the desired zinc aminoacid halide, although an excess of one material or another may bedesirable in certain formulations, e.g., to balance pH against otherformulation constituents, to provide additional antibacterial zinc, orto provide amino acid buffer. Preferably, however, the amount of halideis limited, as constraining the level of halide somewhat encouragesinteraction between the zinc and the amino acid.

In some embodiments, the total amount of zinc in the composition is 0.05to 8% by weight of the composition. In other embodiments, the totalamount of zinc is at least 0.1, at least 0.2, at least 0.3, at least0.4, at least 0.5, or at least 1 up to 8% by weight of the composition.In other embodiments, the total amount of zinc in the composition isless than 5, less than 4, less than 3, less than 2, or less than 1 to0.05% by weight of the composition.

In certain embodiments, a molar ratio of zinc to amino acid is at least2:1. In other embodiments, the molar ratio is at least 1:1, at least1:2, at least 1:3, at least 1:4, 2:1 to 1:4, 1:1 to 1:4, 1:2 to 1:4, 1:3to 1:4, 2:1 to 1:3, 2:1 to 1:2, 2:1 to 1:1, or 1:3. Above 1:4, it isexpected that the zinc will be totally dissolved.

In certain embodiments, the composition is anhydrous. By anhydrous,there is less than 5% by weight water, optionally less than 4, less than3, less than 2, less than 1, less than 0.5, less than 0.1 down to 0% byweight water.

When provided in an anhydrous composition, precursors, e.g., TBZC andamino acid hydrohalide, will not significantly react to form the zincamino acid halide. When contacted with a sufficient amount of water,which can be in the form of saliva and/or water used to rinse the mouthduring or after application of the composition, the precursors will thenreact to form the zinc amino acid halide, then upon further dilution,will provide the zinc-containing precipitate to the teeth.

The carrier represents all other materials in the composition other thanthe zinc amino acid halide complex or its precursors. The amount ofcarrier is then the amount to reach 100% by adding to the weight of thezinc amino acid halide, including any precursors.

Active Agents:

The compositions of the invention may comprise various agents which areactive to protect and enhance the strength and integrity of the enameland tooth structure and/or to reduce bacteria and associated tooth decayand/or gum disease, including or in addition to the zinc-aminoacid-halide complexes. Effective concentration of the active ingredientsused herein will depend on the particular agent and the delivery systemused. It is understood that a toothpaste for example will typically bediluted with water upon use, while a mouth rinse typically will not be.Thus, an effective concentration of active in a toothpaste willordinarily be 5-15× higher than required for a mouth rinse. Theconcentration will also depend on the exact salt or polymer selected.For example, where the active agent is provided in salt form, thecounterion will affect the weight of the salt, so that if the counterionis heavier, more salt by weight will be required to provide the sameconcentration of active ion in the final product. Arginine, wherepresent, may be present at levels from, e.g., about 0.1 to about 20 wt %(expressed as weight of free base), e.g., about 1 to about 10 wt % for aconsumer toothpaste or about 7 to about 20 wt % for a professional orprescription treatment product. Fluoride where present may be present atlevels of, e.g., about 25 to about 25,000 ppm, for example about 750 toabout 2,000 ppm for a consumer toothpaste, or about 2,000 to about25,000 ppm for a professional or prescription treatment product. Levelsof antibacterial agents will vary similarly, with levels used intoothpaste being e.g., about 5 to about 15 times greater than used inmouthrinse. For example, a triclosan toothpaste may contain about 0.3 wt% triclosan.

Fluoride Ion Source:

The oral care compositions may further include one or more fluoride ionsources, e.g., soluble fluoride salts. A wide variety of fluorideion-yielding materials can be employed as sources of soluble fluoride inthe present compositions. Examples of suitable fluoride ion-yieldingmaterials are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S.Pat. No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154,to Widder et al. Representative fluoride ion sources include, but arenot limited to, stannous fluoride, sodium fluoride, potassium fluoride,sodium monofluorophosphate, sodium fluorosilicate, ammoniumfluorosilicate, amine fluoride, ammonium fluoride, and combinationsthereof. In certain embodiments the fluoride ion source includesstannous fluoride, sodium fluoride, sodium monofluorophosphate as wellas mixtures thereof. In certain embodiments, the oral care compositionof the invention may also contain a source of fluoride ions orfluorine-providing ingredient in amounts sufficient to supply about 25ppm to about 25,000 ppm of fluoride ions, generally at least about 500ppm, e.g., about 500 to about 2000 ppm, e.g., about 1000 to about 1600ppm, e.g., about 1450 ppm. The appropriate level of fluoride will dependon the particular application. A toothpaste for general consumer usewould typically have about 1000 to about 1500 ppm, with pediatrictoothpaste having somewhat less. A dentifrice or coating forprofessional application could have as much as about 5,000 or even about25,000 ppm fluoride. Fluoride ion sources may be added to thecompositions of the invention at a level of about 0.01 wt. % to about 10wt. % in one embodiment or about 0.03 wt. % to about 5 wt. %, and inanother embodiment about 0.1 wt. % to about 1 wt. % by weight of thecomposition in another embodiment. Weights of fluoride salts to providethe appropriate level of fluoride ion will obviously vary based on theweight of the counterion in the salt.

Amino Acids:

In some embodiments, the compositions of the invention comprise an aminoacid. In particular embodiments, the amino acid may be a basic aminoacid. By “basic amino acid” is meant the naturally occurring basic aminoacids, such as arginine, lysine, and histidine, as well as any basicamino acid having a carboxyl group and an amino group in the molecule,which is water-soluble and provides an aqueous solution with a pH ofabout 7 or greater. Accordingly, basic amino acids include, but are notlimited to, arginine, lysine, citrulline, ornithine, creatine,histidine, diaminobutanoic acid, diaminoproprionic acid, salts thereofor combinations thereof. In a particular embodiment, the basic aminoacids are selected from arginine, citrulline, and ornithine. In certainembodiments, the basic amino acid is arginine, for example, 1-arginine,or a salt thereof.

In various embodiments, the amino acid is present in an amount of about0.5 wt. % to about 20 wt. % of the total composition weight, about 0.5wt. % to about 10 wt. % of the total composition weight, for exampleabout 1.5 wt. %, about 3.75 wt. %, about 5 wt. %, or about 7.5 wt. % ofthe total composition weight in the case of a dentifrice, or for exampleabout 0.5-2 wt. %, e.g., about 1% in the case of a mouthwash.

Abrasives:

The compositions of the invention, e.g. Composition 1 et seq. includesilica abrasives, and may comprise additional abrasives, e.g., a calciumphosphate abrasive, e.g., tricalcium phosphate (Ca₃(PO₄)₂),hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂), or dicalcium phosphate dihydrate(CaHPO₄.2H₂O, also sometimes referred to herein as DiCal) or calciumpyrophosphate; calcium carbonate abrasive; or abrasives such as sodiummetaphosphate, potassium metaphosphate, aluminum silicate, calcinedalumina, bentonite or other siliceous materials, or combinationsthereof.

Other silica abrasive polishing materials useful herein, as well as theother abrasives, generally have an average particle size ranging betweenabout 0.1 and about 30 microns, about between 5 and about 15 microns.The silica abrasives can be from precipitated silica or silica gels,such as the silica xerogels described in U.S. Pat. No. 3,538,230, toPader et al. and U.S. Pat. No. 3,862,307, to Digiulio. Particular silicaxerogels are marketed under the trade name Syloid® by the W. R. Grace &Co., Davison Chemical Division. The precipitated silica materialsinclude those marketed by the J. M. Huber Corp. under the trade nameZeodent®, including the silica carrying the designation Zeodent 115 and119. These silica abrasives are described in U.S. Pat. No. 4,340,583, toWason. In certain embodiments, abrasive materials useful in the practiceof the oral care compositions in accordance with the invention includesilica gels and precipitated amorphous silica having an oil absorptionvalue of less than about 100 cc/100 g silica and in the range of about45 cc/100 g to about 70 cc/100 g silica. Oil absorption values aremeasured using the ASTA Rub-Out Method D281. In certain embodiments, thesilicas are colloidal particles having an average particle size of about3 microns to about 12 microns, and about 5 to about 10 microns. Low oilabsorption silica abrasives particularly useful in the practice of theinvention are marketed under the trade designation Sylodent XWA® byDavison Chemical Division of W.R. Grace & Co., Baltimore, Md. 21203.Sylodent 650 XWA®, a silica hydrogel composed of particles of colloidalsilica having a water content of 29% by weight averaging about 7 toabout 10 microns in diameter, and an oil absorption of less than about70 cc/100 g of silica is an example of a low oil absorption silicaabrasive useful in the practice of the present invention.

Foaming Agents:

The oral care compositions of the invention also may include an agent toincrease the amount of foam that is produced when the oral cavity isbrushed. Illustrative examples of agents that increase the amount offoam include, but are not limited to polyoxyethylene and certainpolymers including, but not limited to, alginate polymers. Thepolyoxyethylene may increase the amount of foam and the thickness of thefoam generated by the oral care carrier component of the presentinvention. Polyoxyethylene is also commonly known as polyethylene glycol(“PEG”) or polyethylene oxide. The polyoxyethylenes suitable for thisinvention will have a molecular weight of about 200,000 to about7,000,000. In one embodiment the molecular weight will be about 600,000to about 2,000,000 and in another embodiment about 800,000 to about1,000,000. Polyox® is the trade name for the high molecular weightpolyoxyethylene produced by Union Carbide. The polyoxyethylene may bepresent in an amount of about 1% to about 90%, in one embodiment about5% to about 50% and in another embodiment about 10% to about 20% byweight of the oral care carrier component of the oral care compositionsof the present invention. Where present, the amount of of foaming agentin the oral care composition (i.e., a single dose) is about 0.01 toabout 0.9% by weight, about 0.05 to about 0.5% by weight, and in anotherembodiment about 0.1 to about 0.2% by weight.

Surfactants:

The compositions useful in the invention may contain anionicsurfactants, for example:

-   -   i. water-soluble salts of higher fatty acid monoglyceride        monosulfates, such as the sodium salt of the monosulfated        monoglyceride of hydrogenated coconut oil fatty acids such as        sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride        sulfate,    -   ii. higher alkyl sulfates, such as sodium lauryl sulfate,    -   iii. higher alkyl-ether sulfates, e.g., of formula        CH₃(CH₂)_(m)CH₂(OCH₂CH₂)_(n)OSO₃X, wherein m is 6-16, e.g., 10,        n is 1-6, e.g., 2, 3 or 4, and X is Na or K, for example sodium        laureth-2 sulfate (CH₃(CH₂)₁₀CH₂(OCH₂CH₂)₂OSO₃Na).    -   iv. higher alkyl aryl sulfonates such as sodium dodecyl benzene        sulfonate (sodium lauryl benzene sulfonate)    -   v. higher alkyl sulfoacetates, such as sodium lauryl        sulfoacetate (dodecyl sodium sulfoacetate), higher fatty acid        esters of 1,2 dihydroxy propane sulfonate, sulfocolaurate        (N-2-ethyl laurate potassium sulfoacetamide) and sodium lauryl        sarcosinate.

By “higher alkyl” is meant, e.g., C₆₋₃₀ alkyl. In particularembodiments, the anionic surfactant is selected from sodium laurylsulfate and sodium ether lauryl sulfate. The anionic surfactant may bepresent in an amount which is effective, e.g., >0.01% by weight of theformulation, but not at a concentration which would be irritating to theoral tissue, e.g., <10%, and optimal concentrations depend on theparticular formulation and the particular surfactant. For example,concentrations used or a mouthwash are typically on the order of onetenth that used for a toothpaste. In one embodiment, the anionicsurfactant is present in a toothpaste at from about 0.3% to about 4.5%by weight, e.g., about 1.5%. The compositions of the invention mayoptionally contain mixtures of surfactants, e.g., comprising anionicsurfactants and other surfactants that may be anionic, cationic,zwitterionic or nonionic. Generally, surfactants are those which arereasonably stable throughout a wide pH range. Surfactants are describedmore fully, for example, in U.S. Pat. No. 3,959,458, to Agricola et al.;U.S. Pat. No. 3,937,807, to Haefele; and U.S. Pat. No. 4,051,234, toGieske et al. In certain embodiments, the anionic surfactants usefulherein include the water-soluble salts of alkyl sulfates having about 10to about 18 carbon atoms in the alkyl radical and the water-solublesalts of sulfonated monoglycerides of fatty acids having about 10 toabout 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinateand sodium coconut monoglyceride sulfonates are examples of anionicsurfactants of this type. In a particular embodiment, the composition ofthe invention, e.g., Composition 1, et seq., comprises sodium laurylsulfate.

The surfactant or mixtures of compatible surfactants can be present inthe compositions of the present invention in about 0.1% to about 5.0%,in another embodiment about 0.3% to about 3.0% and in another embodimentabout 0.5% to about 2.0% by weight of the total composition.

Tartar Control Agents:

In various embodiments of the present invention, the compositionscomprise an anticalculus (tartar control) agent. Suitable anticalculusagents include without limitation phosphates and polyphosphates (forexample pyrophosphates), polyaminopropanesulfonic acid (AMPS),hexametaphosphate salts, zinc citrate trihydrate, polypeptides,polyolefin sulfonates, polyolefin phosphates, diphosphonates. Theinvention thus may comprise phosphate salts. In particular embodiments,these salts are alkali phosphate salts, i.e., salts of alkali metalhydroxides or alkaline earth hydroxides, for example, sodium, potassiumor calcium salts. “Phosphate” as used herein encompasses orallyacceptable mono- and polyphosphates, for example, P₁₋₆ phosphates, forexample monomeric phosphates such as monobasic, dibasic or tribasicphosphate; dimeric phosphates such as pyrophosphates; and multimericphosphates, e.g., sodium hexametaphosphate. In particular examples, theselected phosphate is selected from alkali dibasic phosphate and alkalipyrophosphate salts, e.g., selected from sodium phosphate dibasic,potassium phosphate dibasic, dicalcium phosphate dihydrate, calciumpyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate,sodium tripolyphosphate, and mixtures of any of two or more of these. Ina particular embodiment, for example the compositions comprise a mixtureof tetrasodium pyrophosphate (Na₄P₂O₇), calcium pyrophosphate (Ca₂P₂O₇),and sodium phosphate dibasic (Na₂HPO₄), e.g., in amounts of ca. 3-4% ofthe sodium phosphate dibasic and ca. 0.2-1% of each of thepyrophosphates. In another embodiment, the compositions comprise amixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate(STPP)(Na₅P₃O₁₀), e.g., in proportions of TSPP at about 1-2% and STPP atabout 7% to about 10%. Such phosphates are provided in an amounteffective to reduce erosion of the enamel, to aid in cleaning the teeth,and/or to reduce tartar buildup on the teeth, for example in an amountof 2-20%, e.g., ca. 5-15%, by weight of the composition.

Flavoring Agents:

The oral care compositions of the invention may also include a flavoringagent. Flavoring agents which are used in the practice of the presentinvention include, but are not limited to, essential oils as well asvarious flavoring aldehydes, esters, alcohols, and similar materials.Examples of the essential oils include oils of spearmint, peppermint,wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon,lemon, lime, grapefruit, and orange. Also useful are such chemicals asmenthol, carvone, and anethole. Certain embodiments employ the oils ofpeppermint and spearmint. The flavoring agent may be incorporated in theoral composition at a concentration of about 0.1 to about 5% by weighte.g. about 0.5 to about 1.5% by weight.

Polymers:

The oral care compositions of the invention may also include additionalpolymers to adjust the viscosity of the formulation or enhance thesolubility of other ingredients. Such additional polymers includepolyethylene glycols, polysaccharides (e.g., cellulose derivatives, forexample carboxymethyl cellulose, or polysaccharide gums, for examplexanthan gum or carrageenan gum). Acidic polymers, for examplepolyacrylate gels, may be provided in the form of their free acids orpartially or fully neutralized water soluble alkali metal (e.g.,potassium and sodium) or ammonium salts.

Silica thickeners, which form polymeric structures or gels in aqueousmedia, may be present. Note that these silica thickeners are physicallyand functionally distinct from the particulate silica abrasives alsopresent in the compositions, as the silica thickeners are very finelydivided and provide little or no abrasive action. Other thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethylcellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gumssuch as karaya, gum arabic, and gum tragacanth can also be incorporated.Colloidal magnesium aluminum silicate can also be used as component ofthe thickening composition to further improve the composition's texture.In certain embodiments, thickening agents in an amount of about 0.5% toabout 5.0% by weight of the total composition are used.

The compositions of the invention may include an anionic polymer, forexample in an amount of from about 0.05 to about 5%. Such agents areknown generally for use in dentifrice, although not for this particularapplication, useful in the present invention are disclosed in U.S. Pat.Nos. 5,188,821 and 5,192,531; and include synthetic anionic polymericpolycarboxylates, such as 1:4 to 4:1 copolymers of maleic anhydride oracid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether/maleic anhydride having a molecular weight(M.W.) of about 30,000 to about 1,000,000, most preferably about 300,000to about 800,000. These copolymers are available for example as Gantrez.e.g., AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97Pharmaceutical Grade (M.W. 700,000) available from ISP Technologies,Inc., Bound Brook, N.J. 08805. The enhancing agents when present arepresent in amounts ranging from about 0.05 to about 3% by weight. Otheroperative polymers include those such as the 1:1 copolymers of maleicanhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000 and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.Suitable generally, are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrylacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility. Afurther class of polymeric agents includes a composition containinghomopolymers of substituted acrylamides and/or homopolymers ofunsaturated sulfonic acids and salts thereof, in particular wherepolymers are based on unsaturated sulfonic acids selected fromacrylamidoalykane sulfonic acids such as 2-acrylamide 2 methylpropanesulfonic acid having a molecular weight of about 1,000 to about2,000,000, described in U.S. Pat. No. 4,842,847, Jun. 27, 1989 to Zahid.Another useful class of polymeric agents includes polyamino acidscontaining proportions of anionic surface-active amino acids such asaspartic acid, glutamic acid and phosphoserine, e.g. as disclosed inU.S. Pat. No. 4,866,161 Sikes et al.

Water:

The oral compositions may comprise significant levels of water. Wateremployed in the preparation of commercial oral compositions should bedeionized and free of organic impurities. The amount of water in thecompositions includes the free water which is added plus that amountwhich is introduced with other materials.

Humectants:

Within certain embodiments of the oral compositions, it is alsodesirable to incorporate a humectant to prevent the composition fromhardening upon exposure to air. Certain humectants can also impartdesirable sweetness or flavor to dentifrice compositions. Suitablehumectants include edible polyhydric alcohols such as glycerine,sorbitol, xylitol, propylene glycol as well as other polyols andmixtures of these humectants. In one embodiment of the invention, theprincipal humectant is glycerin, which may be present at levels ofgreater than 25%, e.g. 25-35% about 30%, with 5% or less of otherhumectants.

Other Optional Ingredients:

In addition to the above-described components, the embodiments of thisinvention can contain a variety of optional dentifrice ingredients someof which are described below. Optional ingredients include, for example,but are not limited to, adhesives, sudsing agents, flavoring agents,sweetening agents, additional antiplaque agents, abrasives, and coloringagents. These and other optional components are further described inU.S. Pat. No. 5,004,597, to Majeti; U.S. Pat. No. 3,959,458 to Agricolaet al. and U.S. Pat. No. 3,937,807, to Haefele, all being incorporatedherein by reference.

Unless stated otherwise, all percentages of composition components givenin this specification are by weight based on a total composition orformulation weight of 100%.

Unless otherwise specifically identified, the ingredients for use in thecompositions and formulations of the present invention are preferablycosmetically acceptable ingredients. By “cosmetically acceptable” ismeant suitable for use in a formulation for topical application to humanskin. A cosmetically acceptable excipient, for example, is an excipientwhich is suitable for external application in the amounts andconcentrations contemplated in the formulations of this invention, andincludes for example excipients which are “Generally Recognized as Safe”(GRAS) by the United States Food and Drug Administration.

The compositions and formulations as provided herein are described andclaimed with reference to their ingredients, as is usual in the art. Aswould be evident to one skilled in the art, the ingredients may in someinstances react with one another, so that the true composition of thefinal formulation may not correspond exactly to the ingredients listed.Thus, it should be understood that the invention extends to the productof the combination of the listed ingredients.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight. The amounts given are based on the active weightof the material.

EXAMPLES Example 1

The general reaction for formation of ZLC is as follows:ZnO+2(Lysine.HCl)→[Zn(Lysine)₂Cl]Cl.2H₂O(ZLC)A 2:1 molar ratio of ZnO:Lysine.HCl suspension is prepared with stirringat room temperature for about 12 hours. The mixture is centrifuged. 1 mlof supernatant is transferred into an NMR tube. The NMR tube is thenplaced in a closed test tube filled with ethanol for crystal growth. Anumber of colorless, cubic crystals are formed after a week. The crystalstructure of ZLC crystal is determined by single crystal X-raydiffraction. The dimension of this complex molecule is 1.7 nm*7.8 nm*4.3nm. In this complex, Zn cation is coordinated by two two lysine ligandswith two N atoms from NH₂ groups and O atoms from carboxylic groups inan equatorial plane. It displays a distorted square-pyramidal geometrywith the apical position occupied by a Cl atom. This novel structuregives rise to a positive cation moiety, to which a Cl anion is combinedto form an ionic salt.

Laboratory Scale-Up Synthesis of Pure ZLC Powder:

2 mole of LysineHCl is dissolved in 1000 ml DI water with stirring atroom temperature, 1 mole of solid ZnO is added slowly to the LysineHClsolution with stirring and the stirring is continued at RT overnight(about 12 hours). The suspension solution is centrifuged at high speedfor 15 mins. The supernatant is slowly poured into EtOH. A precipitateis formed immediately. Approximately 5-8 ml EtOH is needed to get 1 gpowder. The EtOH solvent with powder is filtered, and an off-whitepowder is obtained. The powder is placed in a 50° C. oven for drying andan 88% yield of product is obtained. PXRD confirms the purity of ZLCpowder compared to ZLC crystal.

Example 2

Four 500 g mouthwash batches which contain NaF, ZLC, ZnCl₂ and ZnO asactive ingredient are formulated with the ingredients shown in Table 1.The objective of this study is to compare the clarity of samples withdifferent actives. Turbidity is evaluated by the percent transmission oflight through the solution as measured by a TurbiScan® dispersionstability analyzer. The higher the percent transmission, the moretransparent the. Thus, a smaller percent transmission suggests that thesolution is more turbid. The concentration of zinc ions in ZLC solutionis 25300 ppm obtained by ICP (Inductively Coupled Plasma) analysis,which corresponds to approximately 17% weight of ZLC actives in thesolution. Zinc ion concentration in all batches is controlled to samelevel, i.e., 1.01 wt %. Among the four batches, the one that has ZnO asactive appears milk white, with 0% transmission, while the other threesamples are as clear as the deionized water (Table 2).

TABLE 1 Ingredients % Loading (g) Actual (g) Mouthwash with NaF Sorbitol70% sol 5.5 27.5 27.51 Sodium Fluoride 0.05 0.25 0.25 Na Saccharin 0.020.1 0.1 Propylene Glycol 7 35 35 Poloxomer 407 0.4 2 2.01 Citric Acid0.02 0.1 0.1 Potassium Sorbitol 0.05 0.25 0.25 Glycerin 7.5 37.5 37.5Peppermint Flavor 0.1 0.5 0.5 Deionized water 79.36 396.8 396.8 Total100 500 500.02 Mouthwash with ZnCl2 Sorbitol 70% sol 5.5 27.5 27.5 ZnCl247.97% Zn 2.11 10.55 10.56 Na Saccharin 0.02 0.1 0.1 Propylene Glycol 735 34.98 Poloxomer 407 0.4 2 2 Citric Acid 0.02 0.1 0.1 PotassiumSorbitol 0.05 0.25 0.25 Glycerin 7.5 37.5 37.48 Peppermint Flavor 0.10.5 0.48 Deionized water 77.3 386.5 386.88 Total 100 500 500.33 Zn %1.01 Mouthwash with ZnO Sorbitol 70% sol 5.50 27.5 27.55 ZnO 80.34% Zn1.26 6.3 6.28 Na Saccharin 0.02 0.1 0.1 Propylene Glycol 7 35 34.98Poloxomer 407 0.4 2 2.02 Citric Acid 0.02 0.1 0.1 Potassium Sorbitol0.05 0.25 0.25 Glycerin 7.5 37.5 37.52 Peppermint Flavor 0.1 0.5 0.52Deionized water 78.15 390.75 390.62 Total 100 500 499.94 Zn % 1.01Mouthwash with ZLC Sorbitol 70% sol 5.5 27.5 27.49 ZLC 2.53% Zn 40 200200 Na Saccharin 0.02 0.1 0.1 Proylene Glycol 7 35 35.01 Poloxomer 4070.4 2 2 Citric Acid 0.02 0.1 0.1 Potassium Sorbitol 0.05 0.25 0.25Glycerin 7.5 37.5 37.5 Peppermint Flavor 0.1 0.5 0.5 Deionized water39.41 197.05 196.98 Total 100 500 499.93 Zn % 1.01

TABLE 2 DI NaF ZLC ZnCl₂ ZnO water MW MW MW MW pH 5.89 4.79 7.18 3.497.03 Turbidity 88.68% 88.40% 86.23% 89.03 0.0016% (% Transmission)

All original mouthwash batches are diluted into 2 fold, 4 fold, 8 fold,16 fold and 32 fold. Turbidity measurements are performed after allsolutions are prepared and well shaken. The turbidity data of thesamples are shown in Table 3, 4, 5 and 6, for the dilutions of mouthwashcontaining NaF, ZLC, ZnCl₂ and ZnO respectively. Precipitation isobserved as ZLC mouthwash sample is diluted, but the turbidity of theother samples is unchanged.

TABLE 3 2X 4X 8X 16X 32X Turbidity 89.85% 88.90% 88.44% 88.77% 88.61% (%transmission)

TABLE 4 2X 4X 8X 16X 32X pH 7.46 7.67 7.86 7.80 7.94 Turbidity 86.73%85.99% 60.50% 59.61% 23.21% (% transmission)

TABLE 5 2X 4X 8X 16X 32X Turbidity 88.63% 88.04% 87.77% 87.42% 87.99% (%transmission)

TABLE 6 2X 4X 8X 16X 32X Turbidity 0% 0% 0% 0% 0% (% transmission)

The diluted ZLC mouthwash samples are placed in a 37° C. oven over theweekend (about 60 hours) for a stability study. Results are shown inTable 7. Precipitation can be observed started from 4 fold dilution. Thelargest amount of precipitation is found at 16 fold dilution. Theoriginal batch, however, is still stable and does not show precipitationeven being aged for 60 hours.

TABLE 7 0X 2X 4X 8X 16X 32X pH 7.16 7.48 7.65 7.82 7.85 7.95 Turbidity(% 86.16% 86.15% 8.33% 6.37% 0.14% 9.91% transmission)

Compared with the mouthwash batches formulated using ZnCl₂ and ZnO, onlythe formulation with ZLC as active can form a clear, stable solution butgenerate the precipitate when diluted. This ZLC mouthwash formulationhas a neutral pH and is stable at 37° C. The ZLC provides a mouthwashformulation which is stable on the shelf but precipitates at dilutesolution. This formation of insoluble precipitate by dilution allowsformation of “plugs” in dentine tubules, providing benefits forhypersensitivity.

Example 3

The mouthwash formulation of the preceding example using ZLC as activeingredient not only shows competitive clarity with current commercialmouthwash product which contains NaF as active ingredient, but alsoexhibits precipitation ability when diluted by water. This uniqueproperty facilitates anti-sensitive and anti-cavity effects, and it isthus of interest to employ ZLC in a toothpaste product.

An oral gel toothpaste with ZLC as active ingredient is formulated andcompared to other formulations containing ZnCl₂, ZnO, and NaF. Only theZLC formulation shows competitive clarity as current gel phasecontaining NaF. The precipitation property of ZLC gel phase is alsoinvestigated by hydrolysis reaction study, providing evidence that whenthe teeth are being brushed with toothpaste containing ZLC actives, theinsoluble particles formed during brushing can penetrate into the dentintubules and block the tubules resulting to anti-sensitive effect andsignal for the consumer.

Four 500 g gel phase batches which contain NaF (control), ZLC, ZnCl₂ andZnO as active ingredient are formulated with the ingredients shown inTable 8. The clarity of samples with different actives is compared, andthe precipitation characteristic of ZLC gel phase by dilution isevaluated. The concentration of zinc ions in ZLC solution is 25300 ppmobtained by ICP, which in terms gives approximately 17% weight of ZLCactives in the solution. Zinc ion concentration in the following batchesare all prepared at 0.5% (w/w) zinc level.

TABLE 8 Ingredients % Loading (g) Actual (g) Oral gel with ZLC (2.53%Zn) Sorbitol 70% sol 76.03 380.15 380.14 ZLC aqueous 20.00 100 100solution 2.53% Zn Carboxymethyl 0.70 3.5 3.51 cellulose (CMC) andTrimethyl cellulose (TMC) Na Saccharin 0.27 1.35 1.35 Propylene Glycol3.00 15 15 Total 100.00 500 500 % Zn 0.506 0.5060% Oral gel with ZnCl₂(47.97% Zn) Sorbitol 70% sol 80 400 399.99 ZnCl2 47.97% Zn 1.06 5.2755.27 CMC TMC 0.70 3.5 3.5 Na Saccharin 0.27 1.35 1.35 Propylene Glycol 315 14.98 DI water 14.98 74.875 74.91 Total 100 500 500 % Zn 0.508 0.5056Oral gel with ZnO (80.34% Zn) Sorbitol 70% sol 80.2 401 400.99 ZnO80.34% Zn 0.63 3.15 3.15 CMC TMC 0.70 3.5 3.5 Na Saccharin 0.27 1.351.35 Propylene Glycol 3 15 15 DI water 15.2 76 75.99 Total 100 500499.98 % Zn 0.505 0.5062% Oral gel with NaF Sorbitol 70% sol 80.2 401401 NaF 0.76 3.8 3.79 CMC TMC 0.70 3.5 3.51 Na Saccharin 0.27 1.35 1.35Propylene Glycol 3 15 15.01 DI water 15.07 75.35 75.36 Total 100 500500.02

Lambda 25 UV/VIS Spectrometer (PerkinElmer) is used to obtain absorbanceinformation for all samples in order to compare the clarity of gel phasebetween different actives. Absorbance is a logarithmic measure of theamount of light that is absorbed when passing through a substance. Sincethe particles in the gel absorb light, the more particles existing insolution, the more light absorbed by the gel. Thus, a small number ofabsorbance of a gel indicates a higher clarity. The absorbance iscorrected by using deionized (DI) water as the blank solution under thelight source wavelength of 610 nm. ZnO is not dissolved and is suspendedin gel phase resulting a high absorbance. Even though ZnCl₂ is solublein water, the gel phase containing ZnCl₂ appears cloudy. Only the gelphase formulated by ZLC forms a homogenous solution and showscompetitive clarity as the gel phase formulated by NaF. The absorbanceand pH of all samples are shown in Table 9.

TABLE 9 NaF ZLC ZnCl₂ ZnO Absorbance 0.0344 0.1765 0.9204 2.4626 pH 7.637.37 5.25 8.30

Dilution Experiment:

All original gel phase batch are diluted into 2 fold, 4 fold, 8 fold, 16fold and 32 fold. There is a decrease of absorbance as the NaF gel,ZnCl₂ gel, and ZnO gel are further diluted, and an increase ofabsorbance in the further diluted ZLC gel solution. This observationconfirms the formation of precipitate when ZLC gel is being diluted bywater. The pHs of 2 fold, 4 fold, 8 fold, 16 fold, and 32 fold dilutedZLC gel solution are 7.71, 7.91, 8.03, 8.12, and 8.14, respectively.

TABLE 10 Active 2 fold 4 fold 8 fold 16 fold 32 fold Ingredient dilutiondilution dilution dilution dilution NaF 0.0106 0.0104 0.0107 0.00750.0137 ZLC 0.1436 0.1887 0.1860 0.1336 0.2998 ZnCl₂ 0.7315 0.3700 0.17010.0570 0.0280 ZnO 2.4630 2.5340 2.1883 1.8638 1.0492

The above gels can be used alone or in a toothpaste having a gel phaseand an abrasive paste phase. ZLC as active ingredient in gel phase oftoothpaste formulation. Compared with the gel phase batches formulatedby ZnCl₂ and ZnO, only the formulation with ZLC as active showscompetitive clarity and pH as the one used in commercial product (NaF asactive ingredient). The dilution experiment shows that only ZLC gelphase can form insoluble precipitate from transparent gel when it isdiluted. The formation of insoluble precipitate by dilution facilitatesthe formation of “plugs” in dentine tubules after using this type oftoothpaste, and moreover, it provides a white precipitate signal duringconsumer use.

Example 4

Dentinal occlusion by an oral gel with ZLC is measured compared to anoral gel without ZLC for potential anti-hypersensitivity benefit. AFlodec instrument is used to measure fluid flow through dentin tubules.A Pashley cell method (e.g., Pashley D H, O'Meara J A, Kepler E E, etal. Dentin permeability effects of desensitizing dentifrices in vitro. JPeriodontol. 1984; 55(9):522-525) is used following a procedure used tomeasure dentinal occlusion on mouth wash formulations by S. Mello. Two10 minute treatments of 400 μl sample are applied with a pipette ondentin disks at 10 minute intervals. After each treatment the disks arerinsed with phosphate buffered saline (PBS) and measured for flow usinga FLODEC apparatus, a device which tracks the position of a meniscusinside a capillary tube to measure small changes in volume. Table 11shows average flow of the oral gel with ZLC and percent flow reductionafter sample application.

TABLE 11 Average Flow (μl/min) of Oral Gel with ZLC % Flow ReductionBaseline Treatment#2 Difference (from Baseline) Rep#1 7.51 3.47 4.0553.87 Rep#2 13.02 7.20 5.82 44.68 Rep#3 25.74 19.79 5.95 23.13 AVG 40.56STDEV 15.78As shown above, the average percent flow reduction of oral gel with ZLCtriplicates is about 41% through dentin tubules.

Table 12 shows average flow of oral gel without ZLC (control) andpercent flow reduction after sample application.

TABLE 12 Average Flow (μl/min) of Oral Gel without ZLC (Control) % FlowReduction Baseline Treatment#2 Difference (from Baseline) Rep#1 7.255.02 2.23 30.85 Rep#2 13.94 8.43 5.51 39.57 Rep#3 22.84 17.93 4.91 21.53AVG 30.65 STDEV 9.02As shown above, the average percent flow reduction of oral gel withoutZLC triplicates (control) is about 31% through dentin tubules.

The oral gel with ZLC shows directionally better performance, ascompared to the oral gel without ZLC (control) in an in-vitro hydraulicconductance model using a FLODEC apparatus.

Example 5

Various dilutions of ZLC are prepared to evaluate its efficiency inproducing visible precipitates and/or flocculation, which can bedelivered in situ onto an oral surface or into a dental opening, such asopen tubules.

A neat solution of ZLC is prepared by 1), reacting 0.5 mole of ZnOpowder with 1 mole of lysine HCl in 1 liter of water at room temperaturefor about 2 hours, and 2) collecting the supernatant throughcentrifugation followed by filtration using a 0.45 micron membrane. Theneat solution has a zinc concentration of 2.39% by weight, and a pH ofabout 7.03.

Dilution experiment is conducted by mixing the neat solution withdeionized water. The neat solution is diluted by 2×, 4×, 6×, 7×, 8×,10×, 12×, 16×, 20×, 24×, 28×, and 32×, corresponding to initial zincconcentrations of 1.20%, 0.598%, 0.398%, 0.341%, 0.299%, 0.239%, 0.199%,0.149%, 0.120%, 0.0996%, 0.0854%, 0.0747%, by weight, respectively. Thediluted samples are kept at 37° C., and the rates at whichflocculation/precipitation occurred are monitored. Dilutions withinitial zinc concentrations at 0.149% and 0.199% are able to generatesome visible flocculation within 30 minutes from the time point when thestock solution is mixed with water. One hour from mixing, visibleflocculation are observed in dilutions with initial zinc concentrationsof between 0.0854% and 0.239%. One and a half hours after mixing,visible flocculation are observed in dilutions with initial zincconcentrations of between 0.0747% and 0.239%. Two hours after mixing,the additional sample with initial zinc concentration of 0.299% alsoshowed presence of flocculation. After a total of 19 hours, flocculationand/or precipitation can be observed in all samples except the one withinitial zinc concentration of 1.20%, and the ones with initial zincconcentrations of between 0.0747% and 0.239% exhibit the mostprecipitates.

pH values of final diluted samples are suitable for oral careapplications. The samples with initial zinc concentrations of 0.0747%,0.0854%, 0.0996%, 0.120%, 0.149%, 0.199 wt % and 0.239% had a final pHvalue of 7.99, 8.13, 8.11, 7.97, 7.99, 6.80, and 6.70, respectively.These pH values were well within the range of 5.5 to 10, which definesthe suitable range for oral care formulations.

Zinc is present in the precipitates primarily in the form of zinc oxide.Lysine is present in the precipitate as an integral component thereofand/or as an impurity.

Example 6

Confocal images demonstrate the efficiency of ZLC in generating asurface deposits and occluding tubule openings on dentine surface, underconditions where visible precipitation can be formed.

The deposition/occlusion assay is conducted using human dentine slicesand the neat solution of Example 5. The dentine slices were prepared bycutting human tooth into thin dentine sections of about 800 microns inthickness, choosing a test side, sanding said test side using asandpaper of about 600 grit, polishing said test side using a Buehlerpolishing cloth and 5 micron Buehler aluminum oxide, acid-etching saiddentine section in 1% (by weight) citric acid solution for about 20seconds, sonicating said dentine section for 10 minutes, and storingsaid dentine section in phosphate buffered saline (PBS, pH 7.4).

For treatment, the neat solution is diluted 16-fold with water, yieldinga treatment solution with initial zinc concentration of about 0.149% byweight. The dentine section is immersed in the treatment solution for 1hour at 37° C. The treated dentine section is then removed from thetreatment solution, and rinsed 4 times, each time with 1 mL of PBS. Thedentine section is then dried using a paper-based tissue and examinedunder confocal microscope in both XYZ and XYZ modes. Subsequenttreatments are conducted in the same manner.

Progressive deposition and occlusion can be observed via confocalimaging. The first treatment leads to noticeable deposition. The secondtreatment leads to complete surface coverage, including blocking ofsubstantially all tubule openings. The surface deposits can be 10microns or more in thickness. After the third treatment, completesurface coverage and complete blocking of tubule openings are observed.The surface deposits can be 25 microns or more in thickness. Thedeposits impart a white color to the dentine surface.

The surface deposits provide various benefits, including those commonlyassociated with zinc and lysine, as well as protection from erosionthrough the neutralization of erosive acids by the deposits, protectionfrom sensitivity through the blocking of tubules, and controlled releaseof actives due to the gradual release of zinc and lysine from thedeposits, particularly upon acid challenge.

Example 7

Confocal images demonstrate the efficiency of ZLC in generating asurface deposits and occluding tubule openings on dentine surface, underconditions where visible precipitation is not observed.

Dentine sections, as prepared in Example 6, are repeatedly treated withZLC dilutions with initial zinc concentration of 0.0747% by weight. Eachtreatment involved 32 mL of diluted solution (1 mL of neat solution fromExample 5 and 31 mL of deionized water) and lasts for 10 minutes at 37°C., during which time, no precipitation is observed by naked eyes. Thedentine section is examined under the confocal microscope after eachtreatment. After 4 consecutive treatments, significant surfacedeposition is observed. After 12 consecutive treatments, completesurface coverage is observed leaving no sign of presence of tubuleopenings.

Therefore, surface deposition and tubule occlusion can occur underconditions, both in terms of dilution ratios and treatment durations,that do not produce visible precipitation.

Example 8

Test dentifrice comprising zinc-lysine, 1450 ppm fluoride, andphosphates is prepared as described in Table 13:

TABLE 13 Ingredient Wt % PEG600 3 CMC-7 0.65 Xanthan 0.2 Sorbitol 27Glycerin 20 Saccharin 0.3 Tetrasodium pyrophosphate 0.5 Calciumpyrophosphate 0.25 Sodium phosphate dibasic 3.5 Sodium fluoride 0.32 (toprovide 1450 ppm fluoride) Titanium dioxide 0.5 Abrasive silica 8Thickener silica 8 ZLC 7 Sodium lauryl sulfate 1.5 Flavoring 1.2 WaterQS

While the invention has been described with respect to specific examplesincluding presently preferred modes of carrying out the invention, thoseskilled in the art will appreciate that there are numerous variationsand permutations of the above described systems and techniques. It is tobe understood that other embodiments may be utilized and structural andfunctional modifications may be made without departing from the scope ofthe present invention. Thus, the scope of the invention should beconstrued broadly as set forth in the appended claims.

The invention claimed is:
 1. A method of treating or reducing dentalenamel erosion, cleaning the teeth, reducing bacterially-generatedbiofilm and plaque, reducing gingivitis, inhibiting tooth decay andformation of cavities, and/or reducing dentinal hypersensitivity,comprising applying an oral care composition comprising a zinc aminoacid halide complex to the teeth and rinsing with water or aqueoussolution; wherein the amino acid is lysine, and the complex has thechemical structure [Zn(C₆H₁₄N₂O₂)₂Cl]⁺ Cl⁻ in solid salt form,optionally in mono- or dihydrate form; and wherein the composition is inthe form of a toothpaste, powder, cream, strip, or gum.
 2. The method ofclaim 1, wherein the zinc amino acid halide complex is formed fromprecursors.
 3. The method of claim 2, and wherein the precursors are azinc ion source, an amino acid source, and a halide source.
 4. Themethod of claim 2, wherein the halide source can be part of the zinc ionsource, the amino acid source, or a halogen acid.
 5. The method of claim3, wherein the zinc ion source and the amino acid source form a complex.6. The method of claim 1 wherein the amount of zinc in the compositionis 0.05-4% by weight.
 7. The method of claim 1 wherein the zinc issolubilized in the composition, but provides a zinc precipitate upondilution to 1:16 with saliva and/or rinsing.
 8. The method of claim 1,wherein the composition is in the form of a toothpaste.
 9. The method ofclaim 1 wherein the composition further comprises an effective amount ofa fluoride ion source.
 10. The method of claim 1 wherein the compositionfurther comprises an orally acceptable base comprising ingredientsselected from one or more of abrasives, buffering agents, humectants,surfactants, thickeners, gum strips or fragments, breath fresheners,flavoring, fragrance, coloring, antibacterial agents, whitening agents,agents that interfere with or prevent bacterial attachment, calciumsources, phosphate sources, orally acceptable potassium salts, anionicpolymers, and combinations thereof.
 11. The method of claim 1 whereinthe pH of the composition is from pH 6 to pH 8.